Progress 1983 to 1984 includes carcinoma (CA)-associated T and Tn antigens. We found Tn to be the immediate precursor of T. Both are universal human CA markers and autoantigens. In the former role, they are powerful in pathohistological diagnosis and sometimes prognosis, while the autoimmune responses against T allow early CA detection with high sensitivity and specificity. In an in vitro model, we showed T-\and Tn-specific clusters to be strongly involved in CA adhesion to healthy tissue, one of the primary steps of CA invasion. We prepared rat and anti-T and -Tn monoclonal antibodies with desialylated human O red blood cells (RBC). We found that fully desialylated healthy RBC and T antigen isolated therefrom contain Tn-specific, active structures. TBC-derived T antigen (an artifact) thus resembles cell surface structures of well-differentiated CAs, which we recently found to have more T than Tn; the reverse was generally true for anaplastic CAs. The importance of Tn in CA is also shown by our finding that of 12 monoclonal antihuman CA antibodies given by others four were anti-Tn. We found clustering of T and Tn epitopes important for cellular immune responses of CA patients and conformational factors for humoral ones. Contrary to general belief, we detected immunoreactive T and Tn epitopes in human embryos (pretolerant stage). Biochemical studies on T and Tn antigens from healthy human RBC, on guinea pig L-10 hepatoCA, and on a human breast CA culture (approximately 3 x 1011 cells of which we have now grown) resulted in glycopeptide (GP) and glycoplipid (GL) fractions with T, Tn, N, and M activity. From the RBCs, we obtained homogeneous active NH2-terminal penta-, hexa-, and hepta-GPs (approximately 2 kilodaltons) with T-specific clusters and larger, T and Tn active GPs (approximately 12 kilodaltons). From the L-10 Ca cultures, we obtained T and Tn active neutral glycolipids larger than tetrahexaosyl ceramide and N and M active gangliosides. From the breast CA cultures, we obtained active GP and GL; we identified two major T-\and Tn-active GP fractions. T has Gal and GalNAc (O-linked) has a molar ratio of approximately 1.5:1. The Tn-active GP fraction was rich in terminal GalNAc, and Ser and Thr are prominent in both. (AG)